Differential expression of Hsp27 in normal oesophagus, Barrett's metaplasia and oesophageal adenocarcinomas

The protein expression patterns of normal, metaplastic and malignant oesoph ageal tissues were analysed by two-dimensional polyacrylamide get electroph oresis (2D-PAGE) to identify changes associated with Barrett's metaplasia a nd transformation to oesophageal adenocarcinoma. Heat-shock protein 27 (Hsp 27), a small heat-shock protein which is protective against cytotoxic stres ses, was abundant in normal oesophagus. However, Hsp27 expression was marke dly lower in Barrett's metaplasia and oesophageal adenocarcinomas. This wit s confirmed by immunohistochemical analysis. Hsp27 protein was most highly expressed in the upper layers of squamous epithelium and exhibited a patter n of expression that corresponded with the degree of squamous maturation. N orthern and Southern analysis demonstrated Hsp27 to be regulated at the lev el of mRNA transcription or abundance. Normal oesophageal tissues were exam ined for gender differences in Hsp27 expression. Women expressed fourfold h igher levels of Hsp27 mRNA, however, this difference was not appreciable in protein expression. Hsp27 protein was inducible by heat shock in Barrett's adenocarcinoma cell lines and an immortalized oesophageal epithelial cell line (HET-1A), but not by oestradiol. These results demonstrate abundant co nstitutive expression of the stress-response protein Hsp27 in the normal oe sophagus, and suggest that low-level expression in Barrett's metaplasia may be one factor which may influence susceptibility to oesophageal adenocarci noma development.